Arsine oxide substitution products of phenyl-azo-alpha-alpha-diaminopyridine



Patented Oct. 13, 1931 UNITED STATES :imm. OFFICE rumour) 'r. TISZA AND BERNARD :roos, or vo'nxnas, NEW Yorur, ASSIGNORS TO THE PYRIDIUM conrom'rron, or murmur PARK, NEW YORK, A conrom'rron on NEW YORK ARSINE oxnm SUBSTITUTION PRODUCTS or PHENYL-AZO-ALP HA-ALPEA-DIAMINO- rmnmr. a

N0 Drawing.

This invention relates to arsine-oxide substitution products of phenyl-azo-alpha-alpha-diaminopyridine, and to methods of obtaining same.

6 One of the primary objects of the invention is the provision of a method of introducing tri-valent arsenic into phenyl-azo-alphaalpha-diaminopyridine, its homologues, analogues, or substitution products.

Compounds of this type, of which paraarsine-oxide 'phenyl-azo alpha alpha diaminopyridine is the base, are preferably obtained from the hydrochloride, and the hydrochloride is prepared by coupling diazotized l5 amino-phenyl-arsine-oxides with diaminopyridine, in 1 he presence of hydrochloric acid.

The hydrochloride so formed is a brick red to dark brown red micro-crystalline powder, melting with decomposition at a range from 30 about 225 to 235 C. It is soluble in methylalcohol, slightly soluble in cold or hot water, and insoluble in ether, chloroform, acetone and toluol.

The base;

namely, para-arsine-oxidephenyl-azo-alpha alpha diaminopyridine,

like that described in our copending application Serial No. 361,265, of even date herewith has an amphoteric character. That is, I it is able to build salts with acids or with alkalies. WVhen an alkali,as for instance, sodium hydroxide, is added to the aqueous solution of the hydrochloride, the loosely bound acid is first neutralized, and the free base precipitated. Further addition of alkali dissolves the precipitate, and forms the alkali salt.

The alkali salt, as for instance, the sodium salt may be precipitated from its solution by adding an excess of concentrated sodium hydroxide solution. This salt which is in micro-crystalline form, is soluble in methylalcohol, but insoluble in ether, chloroform, acetone or toluol.

The free base, that is, para-arsine-oxidephenyl-azo-alpha alpha diaminopyridine, may be obtained either from the sodium salt solution by precipitation with an acid, or.

from the hydrochloric salt solution by precipitation with an alkali, and it occurs in the form of a yellow powder.

Application filed May 7, 1929. Serial No. 381,266.

; Since the formula for phenyl-azoalphaalpha-diaminopyridine is I and as this compound is prepared through diazotization of p amino phenyl arsineoxide, and coupling it with alpha-alpha-diaminopyridine, the formula of the base mus be the following Inthe above formula the place for the copulation is indicated as the beta position in the pyridine nucleus. In general the azo group will go into para osition to the amino group, or into the ortho,1f the paraposition' is occupied. In this case,the azo group is in para position to one of the amino roups, and in ortho positiontoithe other. i be new compounds will, therefore, be paia arsine-oxidephenyl-azo-alpha-alpha-diaminopyridine, its acid or alkali salts. There is -a possibility that some of the'gamma azo. compound is formed, andthat this isomer is present in the above described preparation. But if present, it is in veryv small amounts. These compounds show a distinct bactericidal action in vitro, and also 'tripanocidal action to a certain extent. They are intended for therapeutical use, and to serve as a startingv material forv theproduction of new substances. These new substances may also be made by using-either substitution products of alpha alpha-diaminopyridine or isomers or' substitution products of p-amino-phenyl-arsineoxide. Therefore, we do not intend to limit ourselves to the above described compounds.

An example of the method of preparing the improvedcompounds is given below Example.P-amino-phenyl arsine oxide to the amount of 6.58 gmsis covered in a beaker with 38.6 cc. hydrochloric acid of 8.87%; Y The mixture is cooled to 14 (1., and diazotized with a solution of 2.54 gms. sodium nitrite in 25 cc. of distilled water. About 22 cc. of the sodium nitrite solution above mentioned is suflicient to bring all of the diazonium salt into solution.

'To the diazonium salt solution, asolution of gms. alpha-alphadiaminopyridine in 50 cc. hydrochloric acid of 20% is added, and the copulation takes place immediately. 1 ;The mixture is then .put aside, and after standinga few hours is filtered on a suction. filter, washedwith water, and dried in a vacuum 10 desiccator. f a

:From the hydrochloric salt as prepared above, the sodium salt may beobtained as previously described, by the addition of sufiifrom either the acid or the al aline salt, in the first instance, by" precipitation with an alkali, and in the second instance, by precipitation with anacid. ,7 g

v What isclairnedas hewi sE- a 1. The method ofobtaining arsine-oxidesubstitution products of phenyl-azo-alphaalpha-diaminopyridine, which consists in diazotizing jp-amino-phenyl-arsine-oxide in acidsolution, andcoupling the 'diazotized P- amino-phenyl arsine-oxide'withalpha-alphwdiaminopyridine. c i I 2. The method'of obtainingarsine-oxidesubstitution products of phenyl azo-alpha- 'alpha-diaminopyridine, which consists in diazotizing; p-amino-phenyl-arsine-oxide in acid solution, and coupling thediazotized p-amino-phenyl arsine-oxide with alpha-alpha-diaminopyridine, dissolving the" resultingacid salt in water and preclpitating the free base with alkali solution; r J i 1 I 3. The method of obtaining arsine-oxidesubstitution products of, phenyl-azo-alphaalpha-diamino-pyridine, which consists in diazo'tizing p amino-phenyl-arsine-oxide in P 40 acidf solution;.'coupling* the diaZotized'p-i amino phenyl arsine-oxide with alpha alphadiarninopyridine; dissolving the resulting acid-salt in water; precipitatin' 'the free base (which is substantially insoluble'in water a by neutralizing the loosely-bound acid wit the calculated' amount of alkali; dissolving the precipitatein dilute alkali; and precipitating the alkali-metal salt by adding an excess of'alkali. v i '7 v 60 4; As anew article of manufacture, paraarsine oxidephenyl} azo -alpha'- alpha-di--. aminopyridine, having the following fornot 'NmOAFo a NH V Signed at Yonkers, in the county of-Westchest'er and State of New York, this 2nd day ofMay,A.D.l929.- EDMOND T. TISZA'.

BERNARD ,JO OS.

cient alkali, and the base ma be Obtained p I p I 7 j 

